5MOJ

Crystal structure of IgE-Fc epsilon 3-4

Summary for 5MOJ

• Entry DOI: 10.2210/pdb5moj/pdb
• Descriptor: Ig epsilon chain C region, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, SULFATE ION, ... (6 entities in total)
• Functional Keywords: immunoglobulin e, antibody, ige, immune system
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 52564.64

Authors

Dore, K.A.,Davies, A.M.,Drinkwater, N.,Beavil, A.J.,MacDonnell, J.M.,Sutton, B.J. (deposition date: 2016-12-14, release date: 2018-01-10, Last modification date: 2024-11-06)

Primary citation

Dore, K.A.,Davies, A.M.,Drinkwater, N.,Beavil, A.J.,McDonnell, J.M.,Sutton, B.J.
Thermal sensitivity and flexibility of the C epsilon 3 domains in immunoglobulin E.
Biochim. Biophys. Acta, 1865:1336-1347, 2017

PubMed Abstract: Immunoglobulin E (IgE) is the antibody that plays a central role in the mechanisms of allergic diseases such as asthma. Interactions with its receptors, FcεRI on mast cells and CD23 on B cells, are mediated by the Fc region, a dimer of the Cε2, Cε3 and Cε4 domains. A sub-fragment lacking the Cε2 domains, Fcε3-4, also binds to both receptors, although receptor binding almost exclusively involves the Cε3 domains. This domain also contains the N-linked glycosylation site conserved in other isotypes. We report here the crystal structures of IgE-Fc and Fcε3-4 at the highest resolutions yet determined, 1.75Å and 2.0Å respectively, revealing unprecedented detail regarding the carbohydrate and its interactions with protein domains. Analysis of the crystallographic B-factors of these, together with all earlier IgE-Fc and Fcε3-4 structures, shows that the Cε3 domains exhibit the greatest intrinsic flexibility and quaternary structural variation within IgE-Fc. Intriguingly, both well-ordered carbohydrate and disordered polypeptide can be seen within the same Cε3 domain. A simplified method for comparing the quaternary structures of the Cε3 domains in free and receptor-bound IgE-Fc structures is presented, which clearly delineates the FcεRI and CD23 bound states. Importantly, differential scanning fluorimetric analysis of IgE-Fc and Fcε3-4 identifies Cε3 as the domain most susceptible to thermally-induced unfolding, and responsible for the characteristically low melting temperature of IgE.

PubMed: 28844738
DOI: 10.1016/j.bbapap.2017.08.005

Experimental method

X-RAY DIFFRACTION (2.26 Å)